Cambridge company’s disease model sheds new light on Huntington’s

11/05/2022

A new disease model – one of the first of its kind to be made commercially available – is being hailed as a key pathfinder in reflecting the genetics of Huntington’s disease.

Stand up and take a bow bit.bio – a Cambridge synthetic biology company working on developing and providing every human cell type at scale, with the aim of transforming the research and medicine landscape.

Based at Babraham Research Campus, bit.bio has launched its ioGlutamatergic Neurons HTT50CAG/WT cells to advance research and accelerate drug discovery in relation to the disease.

It is the pioneer product from bit.bio’s new ioDisease Model portfolio – a range of cells which have specific disease-associated mutations that can replicate human diseases in vitro and be matched to an isogenic wild type control. 

The cells are induced pluripotent stem cell (iPSC)-derived, generated using bit.bio’s opti-oxTM1 precision cellular reprogramming technology in combination with CRISPR/Cas9-based gene editing.

Huntington’s disease is an inherited neurodegenerative condition that affects approximately 5-10 out of every 100,000 people. It is caused by specific mutations in the Huntingtin gene. The mutation negatively impacts a range of neuronal cells in the brain resulting in irreversible damage.

There is no known cure for Huntington’s and the precise underlying mechanisms remain poorly understood. There are limited treatment options for patients that only minimise the impact of symptoms. 

Until now, it has been difficult for scientists to engineer the specific disease-causing mutation in cells. Having the right disease model can facilitate the study of potential mechanisms and identify therapeutic approaches.

By introducing a stable 50 ‘CAG’ repeat mutation in the Huntingtin gene in wild type ioGlutamatergic Neurons, bit.bio has developed a consistent, scalable cell model that replicates the disease in vitro. 

Their ability to rapidly mature to glutamatergic neurons, along with their unprecedented scalability and batch-to-batch reproducibility, also makes them ideally suited to high-throughput screening applications.

Using ioGlutamatergic Neurons HTT50CAG/WT and wild type ioGlutamatergic Neurons (that do not possess the mutation) in drug discovery allows the life science community to study the effects of novel treatments in a disease-relevant system with a genetically matched control. 

Being able to compare data from the disease cell model to those of the genetically matched control offers the potential to identify and investigate the effects of the CAG trinucleotide repeat expansion.

Dr Mark Kotter, CEO and founder at bit.bio, said: “bit.bio's mission is coding cells for novel cures. The launch of our Huntington's disease model provides the industry with an advanced cellular tool to support the study of a devastating condition with high unmet clinical needs.

“Our opti-ox technology allows the development of consistent and scalable biological standards that can support the evolution of a new generation of medicines. It adds depth to our broadening R & D cell type product pipeline, each product will transition to its own product line.”

bit.bio’s precision cellular reprogramming technology, opti-ox, enables the controlled reprogramming of entire cultures of stem cells into any cell type. This overcomes the inherent limitations of classical cell generation methods and allows the reproducible production of human cells within days, at an industrial scale.

bit.bio combines the concepts of coding and biology to provide human cells for research, drug discovery and cell therapy, enabling a new generation of medicines.

bit.bio was founded in 2016 by Dr Kotter from his labs at Cambridge University after his discovery of the opti-ox technology. Co-founder Florian Schuster joined in 2018 as the company continued to grow and develop.

The company now has over 130 employees and is headquartered in Cambridge UK and San Francisco in the US.

In July 2019, the company closed a $45 million Series A fundraise, followed by $103m in its first Series B close in November 2021. It recently expanded its already impressive board be recruiting a trio of big-hitters in Dr Hermann Hauser, Sir Greg Winter and Alan S.Roemer.

Dr Hauser, a serial entrepreneur, co-founder of Amadeus Capital Partners and founder of semiconductor company Arm and gene-sequencing business Solexa – sold to US giant Illumina – became chair.

Sir Greg Winter, a Nobel-winning scientist known for his work on monoclonal antibodies, also joined the board; he is the founder of multiple successful biotech companies.

Alan Roemer is a biotechnology entrepreneur who launched Pharmasset and Roivant Sciences; he has helped raise over $1.75 billion in private and public capital and consummated five IPOs.

Published: 10.05.22